As the method for producing an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative and salt thereof, the following examples are known.
(1) A method for producing 3-amino-2-hydroxy-hexanoic cyclopropylamide hydrochloride, wherein L-N-(tert-butoxycarbonyl)-norvaline is reacted with N,O-dimethylhydroxyamine in the presence of a condensing agent to obtain Weinreb amide; the amide is reduced into an aldehyde; cyclopropylisonitrile is added thereto to give (2S,3S)-3-N-tert-butoxycarbonylamino-2-acetoxyhexanoic cyclopropylamide; then the acetyl group and the tert-butoxycarbonyl group are cleavaged (Patent Reference 1, Patent Reference 2).
(2) A method for producing (2S,3S)-3-amino-2-hydroxy-hexanoic cyclopropylamide, wherein hydrocyanic acid is added to an aldehyde derived from L-N-(tert-butoxycarbonyl)-norvaline; then the tert-butoxycarbonyl group is cleavaged and the cyano group is hydrolyzed to give 3-amino-2-hydroxy-hexanoic acid; the nitrogen is protected with benzyloxycarbonyl group; then the protected acid is condensed with cyclopropylamine using a condensing agent and is hydrogenolyzed (Patent Reference 3, Non-Patent Reference 1).
However, the method (1) could not be said to be a realistic method, since expensive L-N-(tert-butoxycarbonyl)-norvaline is used as the starting material, expensive and dangerous lithiumaluminium hydride is used in the reduction step, and a hardly-available isonitrile derivative is used in the step of carbon increase for the aldehyde.
Also, the method (2) is not economical and is difficult to be industrially carried out and could not be said to be an efficient synthetic method, since an expensive L-N-(tert-butoxycarbonyl)-norvaline derivative is used as the starting material, a deadly poisonous hydrocyanic acid is used, and the number of the process steps are increased because of the repetition of protection and deprotection on the nitrogen atom.
Consequently, all of the production methods for an optically-active 3-amino-2-hydroxypropionic cyclopropylamide derivative and salt thereof known at present have a serious problem in point of the economical aspect, and are not practicable from the viewpoint of industrial practicability.
Patent Reference 1: WO2005/058821
Patent Reference 2: US2005/0197301
Patent Reference 3: WO2005/035525
Non-Patent Reference 1: Letters in Drug Design & Discovery, 2005, 118-123